Experiments will be done to study the immune status in three models of specific unresponsiveness and to try to elucidate the mechanisms underlying the unresponsiveness. Both thymectomized and non-thymectomized mice treated with ALS and low doses of donor bone marrow are unresponsive to donor antigens as shown by prolonged skin allograft survival. These mice are not chimeras, they exhibit cell-mediated immunity (CMI) against donor antigens and blocking factors (SBF) are present in their serum. In contrast, thymectomized ALS-treated mice injected with large doses of hybrid lymph node-spleen cells are chimeras and have no evidence of CMI and SBF specific for donor antigens. Experiments will compare these models with reference to (1) presence of suppressor cells in host lymphoid organs and ability of these cells to transfer unresponsiveness to secondary syngeneic recipients (2) role of the thymus in inducing unresponsiveness (3) role of anti-receptor site antibody in unresponsive-states (4) correlation of cells infiltrating grafts on unresponsive mice with histological study of grafts. Other experiments will investigate the ability of platelets and blood transfusions to induce unresponsiveness in ALS-treated mice. Other studies will involve the effect of donor marrow infusion on canine renal allograft survival in ALS-treated dogs.